Pressure provides an additional thermodynamic variable for the study of macromolecular stability. A pressure perturbation will displace the conformational equilibrium of a macromolecule according to the relative volume of each conformation. Pressure is capable not only of affecting the stability of a protein without introducing a chemical variable, but is also able to stabilize selected partially folded conformations. As such, it should become an important instrument for the study of protein stability and folding mechanisms. A differential scanning calorimeter with the capability of operating at different constant pressures represent a long term design plan for the Biocalorimetry Center. During the current year, initial feasibility studies were initiated. It is visualized that this development will be made in two stages. In the first stage a DSC with reinforced cell capable of sustaining up to ~500 atm will be developed. In the second phase, a calorimeter in which the interior as well as the exterior of the cell are pressurized will be designed. This second instrument will be capable of sustaining pressures approaching 4,000 atm